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变应性鼻炎患者外周血淋巴细胞毒蕈碱胆碱能受体表达的变化

Changes in muscarinic cholinergic receptor expression in human peripheral blood lymphocytes in allergic rhinitis patients.

作者信息

Ricci Alberto, Mariotta Salvatore, Amenta Francesco, Tayebati Seyed Khosrow, Terzano Claudio

机构信息

Dipartimento di Scienze Cardiovascolari e Respiratorie, Università di Roma La Sapienza, Rome, Italy.

出版信息

Pulm Pharmacol Ther. 2008;21(1):79-87. doi: 10.1016/j.pupt.2006.12.006. Epub 2007 Jan 17.

DOI:10.1016/j.pupt.2006.12.006
PMID:17360208
Abstract

BACKGROUND

Parasympathetic nerves provide the dominant autonomic innervation of the upper and lower airways. They release acetylcholine that, activating post-junctional muscarinic receptors, causes bronchoconstriction, mucous secretion and vasodilation. Dysfunction of the upper and lower airways frequently coexist, and they appear to share key elements of pathogenesis.

OBJECTIVE

The present study has assessed the expression and pattern of cholinergic muscarinic receptor subtypes in peripheral blood lymphocytes harvested from allergic rhinitis patients with different degree of bronchial hyperresponsiveness detected by methacholine challenge test.

METHODS

Radioligand binding assay for determining the density of muscarinic cholinergic receptor subtypes; immunoblot analysis for assessing the characteristic of muscarinic cholinergic receptor subtype protein and immunocytochemical techniques for investigating the cellular localization of receptors.

RESULTS

An increased expression of M2 and M5 receptor proteins was observed in peripheral blood lymphocytes of allergic rhinitis patients in comparison with healthy control individuals. M3 receptor subtype decreased in allergic rhinitis patients with normal or mild responses to methacholine. A trend versus a return to normal value was found in moderate and severe responders. No changes of the M4 receptor subtype were found.

CONCLUSIONS AND CLINICAL IMPLICATIONS

Increase in M2 receptor expression correlated with disease severity and bronchial hyperreactivity. Changes in muscarinic cholinergic receptor expression in allergic rhinitis underline a role of cholinergic system of immune cells in allergic airway disease.

CAPSULE SUMMARY

Studies addressed to rhinitis and asthma have identified many similarities. Our results indicate that changes in peripheral blood lymphocyte muscarinic receptor expression may reflect the cholinergic involvement into allergic airway diseases.

摘要

背景

副交感神经为上下呼吸道提供主要的自主神经支配。它们释放乙酰胆碱,激活节后毒蕈碱受体,引起支气管收缩、黏液分泌和血管舒张。上下呼吸道功能障碍常同时存在,且似乎具有共同的发病机制关键要素。

目的

本研究评估了从通过乙酰甲胆碱激发试验检测出具有不同程度支气管高反应性的变应性鼻炎患者采集的外周血淋巴细胞中胆碱能毒蕈碱受体亚型的表达及模式。

方法

采用放射性配体结合分析法测定毒蕈碱胆碱能受体亚型的密度;采用免疫印迹分析法评估毒蕈碱胆碱能受体亚型蛋白的特性;采用免疫细胞化学技术研究受体的细胞定位。

结果

与健康对照个体相比,变应性鼻炎患者外周血淋巴细胞中M2和M5受体蛋白表达增加。对乙酰甲胆碱反应正常或轻度的变应性鼻炎患者中M3受体亚型减少。中度和重度反应者呈现出一种趋势,即向正常水平恢复。未发现M4受体亚型有变化。

结论及临床意义

M2受体表达增加与疾病严重程度和支气管高反应性相关。变应性鼻炎中毒蕈碱胆碱能受体表达的变化突显了免疫细胞胆碱能系统在变应性气道疾病中的作用。

综述总结

针对鼻炎和哮喘的研究已发现许多相似之处。我们的结果表明外周血淋巴细胞毒蕈碱受体表达的变化可能反映胆碱能系统参与变应性气道疾病。

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